Combination of 5-azacitidine and Lenalidomide in Myelodysplastic Syndromes (MDS) or Acute Myelogenous Leukemia (AML) Myelodysplastic Syndromes (AZALE)
This study is currently recruiting participants.
Verified June 2011 by Dresden University of Technology
Sponsor:
Dresden University of Technology
Collaborator:
Celgene Corporation
Information provided by:
Dresden University of Technology
ClinicalTrials.gov Identifier:
NCT00923234
First received: June 17, 2009
Last updated: June 24, 2011
Last verified: June 2011
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Purpose
The hypothesis of this study is that 5-aza and lenalidomide act synergistically in MDS and AML patients with chromosomal abnormalities involving monosomy 5 or del5q. Therefore, this phase I study will investigate the maximum tolerated dose (MTD) of lenalidomide in combination with a fixed dose of 5-aza in this patient population.
| Condition | Intervention | Phase |
|---|---|---|
|
Myelodysplastic Syndromes Acute Myelogenous Leukemia |
Drug: Azacitidine Drug: Lenalidomide |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase I Study of a Combination of 5-azacitidine Followed by Lenalidomide in High-risk MDS or Relapsed/Refractory AML Patients With Cytogenetic Abnormalities Including -5 or Del(5q) |
Resource links provided by NLM:
Genetics Home Reference related topics:
familial acute myeloid leukemia with mutated CEBPA
tetrasomy 18p
U.S. FDA Resources
Further study details as provided by Dresden University of Technology:
Primary Outcome Measures:
- Maximum tolerated dose (MTD) of Revlimid® (lenalidomide)in combination with Vidaza®(5-azacitidine) [ Time Frame: during first cycle of therapy ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Clinical and cytogenetic response [ Time Frame: during therapy ] [ Designated as safety issue: No ]
- Safety (type, frequency, severity, and relationship of adverse events to study treatment) [ Time Frame: during therapy ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 30 |
| Study Start Date: | June 2009 |
| Estimated Study Completion Date: | July 2013 |
| Estimated Primary Completion Date: | July 2012 (Final data collection date for primary outcome measure) |
Intervention Details:
Detailed Description:
-
Drug: Azacitidine
75 mg/m² SC days 1-5 every 28 days for a maximum of 8 cycles
Other Name: Vidaza
Drug: Lenalidomide
10 - 25 mg PO days 6-19 every 28 days for a maximum of 8 cycles
Other Name: Revlimid
Cytogenetics are the main predictors of outcome in patients with AML. In fact, a monosomy 5 or del (5q) as single aberration are poor prognostic markers. Overall, the complete response rate for conventionally treated patients with newly-diagnosed AML with chromosome 5 abnormalities is about 31% to 37 % and all patients rapidly relapse if not rescued by allogeneic HSCT. The situation is almost similar in patients with high-risk MDS.Vidaza® has been shown in clinical trials to achieve remission rates in about 29% (CR+PR) of the patients while a total of 49% achieve improvement of blood counts.Revlimid® is also able to achieve complete remissions in advanced MDS and even overt leukemia with or without chromosome 5 abnormalities. Nevertheless, response rates are lower compared to low-risk MDS (IPSS Low/INT-1). Therefore, Revlimid® seems to be too weak as a single agent, but a promising compound for a combination therapy.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Understand and voluntarily sign an informed consent form.
- Age >=18 years at the time of signing the informed consent form.
- Able to adhere to the study visit schedule and other protocol requirements.
- Relapsed or refractory AML (>30% blasts, FAB classification)with karyotype abnormalities involving monosomy 5 or del(5q) or MDS and t-MDS INT-2 or HIGH according to IPSS classification with karyotype abnormalities involving monosomy 5 or del(5q) either previously treated or untreated
- Not eligible for an immediate allogeneic HSCT (due to donor unavailability)
- All previous MDS or AML specific therapy with exception of corticosteroids not exceeding doses of 10mg/day prednisone must have been discontinued at least 1 week prior to study enrollment.
- Non-hematological toxicity (except alopecia) resulting from previous treatment must be resolved to WHO CTC Grade ≤ 2.
- ECOG performance status of < 3 at study entry.
- Laboratory test results within these ranges:Serum creatinine <= 2.0 mg/dL, Total bilirubin <= 3 x ULN, AST (SGOT) and ALT (SGPT) <= 3 x ULN
- Females of childbearing potential must agree to use a reliable form of contraception or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study.
Exclusion Criteria:
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- Pregnant or breast feeding females. (Lactating females must agree not to breast feed while on study).
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- Known hypersensitivity to thalidomide, lenalidomide, 5-azacitidine or mannitol.
- Myocardial infarction within 6 months before study entry, New York Heart Association Class III or IV heart failure, uncontrolled angina or severe uncontrolled ventricular arrhythmias.
- The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
- Uncontrolled lung disease.
- Known positive for HIV or acute infectious hepatitis, type A, B or C.
- Participation in another clinical study in the 4 weeks prior to enrollment or during this study.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00923234
Contacts
| Contact: Uwe Platzbecker, PD Dr. med. | +49 351 4584190 | Uwe.Platzbecker@uniklinikum-dresden.de |
Locations
| Germany | |
| Medizinische Klinik und Poliklinik I, Uniklinik | Recruiting |
| Dresden, Germany | |
| Universitätsklinikum Düsseldorf, Klinik für Hämatologie/Onkologie/klinische Immunologie | Recruiting |
| Düsseldorf, Germany, 40225 | |
| Klinikum der J.W. Goethe-Universität, Medizinische Klink II | Recruiting |
| Frankfurt, Germany, 60590 | |
| Technische Universität München, Klinikum Rechts der Isar | Recruiting |
| München, Germany, 81675 | |
Sponsors and Collaborators
Dresden University of Technology
Celgene Corporation
Investigators
| Principal Investigator: | Uwe Platzbecker, MD | Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus |
More Information
No publications provided
| Responsible Party: | Uwe Platzbecker, PD Dr. med, Universitätsklinikum C. G. Carus an der TU Dresden |
| ClinicalTrials.gov Identifier: | NCT00923234 History of Changes |
| Other Study ID Numbers: | TUD-AZALE1-037 |
| Study First Received: | June 17, 2009 |
| Last Updated: | June 24, 2011 |
| Health Authority: | Germany: Federal Institute for Drugs and Medical Devices |
Keywords provided by Dresden University of Technology:
|
monosomy 5 del5q lenalidomide azacitidine |
Additional relevant MeSH terms:
|
Chromosome Aberrations Leukemia Leukemia, Myeloid, Acute Leukemia, Myeloid Myelodysplastic Syndromes Preleukemia Pathologic Processes Neoplasms by Histologic Type Neoplasms Bone Marrow Diseases Hematologic Diseases Precancerous Conditions Azacitidine Lenalidomide Thalidomide |
Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Leprostatic Agents Anti-Bacterial Agents Anti-Infective Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents |
ClinicalTrials.gov processed this record on May 22, 2013